Department of Pathology, The University of Melbourne, Parkville, VIC 3010, Australia.
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Semin Cancer Biol. 2017 Aug;45:3-12. doi: 10.1016/j.semcancer.2016.07.004. Epub 2016 Aug 1.
As one of the predominant protein families within the extracellular matrix both structurally and functionally, laminins have been shown to be heavily involved in tumor progression and drug resistance. Laminins participate in key cellular events for tumor angiogenesis, cell invasion and metastasis development, including the regulation of epithelial-mesenchymal transition and basement membrane remodeling, which are tightly associated with the phenotypic characteristics of stem-like cells, particularly in the context of cancer. In addition, a great deal of studies and reports has highlighted the critical roles of laminins in modulating stem cell phenotype and differentiation, as part of the stem cell niche. Stemming from these discoveries a growing body of literature suggests that laminins may act as regulators of cancer stem cells, a tumor cell subpopulation that plays an instrumental role in long-term cancer maintenance, metastasis development and therapeutic resistance. The accumulating evidence in this emerging research area suggests that laminins represent potential therapeutic targets for anti-cancer treatments against cancer stem cells, and that they may be used as predictive and prognostic markers to inform clinical management and improve patient survival.
作为细胞外基质中结构和功能上主要的蛋白家族之一,层粘连蛋白已被证明与肿瘤的进展和耐药性密切相关。层粘连蛋白参与肿瘤血管生成、细胞侵袭和转移发展的关键细胞事件,包括调节上皮-间充质转化和基底膜重塑,这与干细胞样细胞的表型特征密切相关,特别是在癌症的背景下。此外,大量的研究和报告强调了层粘连蛋白在调节干细胞表型和分化中的关键作用,作为干细胞巢的一部分。从这些发现中,越来越多的文献表明,层粘连蛋白可能作为癌症干细胞的调节剂,癌症干细胞是肿瘤细胞亚群,在长期癌症维持、转移发展和治疗耐药性中起着重要作用。这一新兴研究领域的累积证据表明,层粘连蛋白可能成为针对癌症干细胞的抗癌治疗的潜在治疗靶点,并且它们可能被用作预测和预后标志物,以告知临床管理并提高患者的生存率。